Pemphigus, pemphigoid and cutaneous lupus
Where the split or deposit sits: antibodies against desmosomes split the epidermis from within in pemphigus, hemidesmosome antibodies lift it off in pemphigoid, IgA lodges in the dermal papillae in dermatitis herpetiformis, and lupus inflames the junction.
By the end, you can
- Describe how desmosomes and the basement membrane zone hold the epidermis together, and which proteins sit where.
- Explain how antibodies against desmogleins cause acantholysis, and use desmoglein compensation to predict where pemphigus vulgaris and foliaceus blister.
- Explain how antibodies against hemidesmosome proteins, complement and eosinophils produce the subepidermal blister of bullous pemphigoid.
- Relate dermatitis herpetiformis to gluten, epidermal transglutaminase and IgA in the dermal papillae.
- Distinguish acute, subacute and chronic discoid cutaneous lupus by appearance, scarring and their link with SLE.
- Read the level of split and the immunofluorescence pattern of each disease, and explain how each main treatment acts on its mechanism.
What it is
Autoimmune blistering diseases are caused by autoantibodies against the proteins that hold the skin together; the level at which the skin splits and the pattern in which antibody is deposited identify the disease. Pemphigus splits the epidermis from within, while bullous pemphigoid and dermatitis herpetiformis separate it from the dermis. Cutaneous lupus inflames the dermal–epidermal junction, with deposits there, usually without a clean split.
3 types to tell apart
- Intraepidermal: the pemphigus group
- IgG against desmogleins: pemphigus vulgaris (desmoglein 3, often with desmoglein 1; mouth and skin) and pemphigus foliaceus (desmoglein 1; skin only).
- Subepidermal
- IgG against hemidesmosome proteins in bullous pemphigoid (and in mucous membrane pemphigoid, which scars); IgA in the dermal papillae in dermatitis herpetiformis; IgA in a line along the basement membrane in linear IgA disease.
- Cutaneous lupus
- Acute (the malar rash of active SLE), subacute (ring-shaped or scaly patches, anti-Ro, rarely scarring) and chronic discoid (scarring plaques, usually without SLE).
Normal function
How the epidermis holds together, and where it can split
Keratinocytes are riveted to each other by desmosomes, button-like junctions whose cadherin proteins, the desmogleins and desmocollins, reach across the gap between cells and are anchored inside to keratin filaments. Two desmogleins matter here. Desmoglein 1 is most plentiful in the upper epidermis, up to the ; desmoglein 3 is concentrated in the and lower , and throughout mucous membranes such as the mouth lining.
The basal cells are fastened to the basement membrane by hemidesmosomes, half-desmosomes that contain BP230 inside the cell and BP180 (type XVII collagen), which crosses the cell membrane into the clear lamina lucida. Below that, the dense lamina densa is tied to the by anchoring fibrils of type VII collagen. Together these form the basement membrane zone, which follows the ridges and papillae.
Each autoimmune blistering disease is an antibody against one of these rivets, so the level of the split points to the target. Antibodies against desmogleins separate cells from each other within the epidermis (intraepidermal); antibodies against the hemidesmosome lift the whole epidermis off the dermis (subepidermal). Immunofluorescence shows where the antibody sits: round every keratinocyte, or along the basement membrane. Cutaneous lupus deposits immunoglobulin at the junction too, but injures it by interface inflammation.
| Feature | Target and antibody | Split or deposit | Direct immunofluorescence |
|---|---|---|---|
| Pemphigus foliaceus | Desmoglein 1 (IgG) | Within the epidermis, just below the stratum corneum | IgG and C3 round every keratinocyte (fishnet) |
| Pemphigus vulgaris | Desmoglein 3, often also 1 (IgG) | Within the epidermis, just above the basal layer | IgG and C3 round every keratinocyte (fishnet) |
| Bullous pemphigoid | BP180 and BP230 of the hemidesmosome (IgG) | Beneath the epidermis, through the lamina lucida | Linear IgG and C3 along the basement membrane |
| Dermatitis herpetiformis | Epidermal transglutaminase (IgA) | Beneath the epidermis, over the dermal papillae | Granular IgA in the papillary tips |
| Cutaneous lupus | Ro and nuclear antigens; cytotoxic T cells | Interface damage at the junction; rarely a split | Granular IgG, IgM and C3 along the junction (lupus band) |
Simplified. Linear IgA disease shows IgA in a line along the basement membrane; mucous membrane pemphigoid targets the same zone as bullous pemphigoid.
Underlying change · Step 1 of 4
Pemphigus: antibodies against desmogleins split the epidermis from within
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 2 of 4
Bullous pemphigoid: antibodies against the hemidesmosome lift the epidermis
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 4
Dermatitis herpetiformis: IgA in the dermal papillae, driven by gluten
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 4 of 4
Cutaneous lupus: interface injury and deposits at the junction
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .